3-benzylamino-2-phenylpiperidines as neurokinin antagonists

Abstract

The invention relates to piperidine derivatives of formula (I) ##STR1## wherein R.sup.1 is a C.sub.2-4 alkoxy group; R.sup.2 is ##STR2## R.sup.3 is a hydrogen or halogen atom; R.sup.4 and R.sup.5 may each independently represent a hydrogen or halogen atom, or a C.sub.1-4 alkyl, C.sub.1-4 alkoxy or trifluoromethyl group;and pharmaceutically acceptable derivatives thereof, to processes for their preparation, and their use in the treatment of conditions mediated by tachykinins.

Claims

1.. A compound of formula (I) ##STR16## wherein R.sup.1 is a C.sub.2-4 alkoxy group; R.sup.2 is ##STR17## R.sup.3 is a hydrogen or halogen atom; R.sup.4 and R.sup.5 may each independently represent a hydrogen or halogen atom, or a C.sub.1-4 alkyl, C.sub.1-4 alkoxy or trifluoromethyl group;

or a pharmaceutically acceptable salt or solvate thereof.

2. A compound according to claim 1 wherein R.sup.3, R.sup.4 and R.sup.5 are hydrogen atoms.

3. A compound according to claim 1 wherein R.sup.1 is an ethoxy, propoxy, prop-2-oxy, butoxy, but-2-oxy, 2-methylprop-1-oxy or 2-methylprop-2-oxy group.

6. A compound according to claim 4 in the form of its dihydrochloride salt.

7. A compound according to claim 1 for use in therapy.

8. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof, together with a pharmaceutically acceptable carrier.

9. A method for the treatment of conditions mediated by tachykinins, including substance P and other neurokinins, in a mammal wherein the conditions are susceptible to treatment by antagonism of tachykinins comprising administration of an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof.

10. A process for preparing a compound of formula (I) as defined in claim 1, or a pharmaceutically acceptable derivative thereof which comprises:

(A) reacting a compound of formula (II) ##STR18## with a compound of formula (III) ##STR19## followed by reduction: or (B) reduction of a compound of formula (IX) ##STR20## with a suitable reducing agent: or (C) reacting a compound of formula (XI) ##STR21## or an amino-protected derivative thereof, with L-C.sub.2-4 alkyl where L represents a suitable leaving group, in the presence of a base, followed by deprotection where necessary.